RGD Reference Report - Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats.

Authors: Watts, JA  Zagorski, J  Gellar, MA  Stevinson, BG  Kline, JA 
Citation: Watts JA, etal., J Mol Cell Cardiol. 2006 Aug;41(2):296-307. Epub 2006 Jun 30.
RGD ID: 11528528
Pubmed: (View Article at PubMed) PMID:16814320
DOI: Full-text: DOI:10.1016/j.yjmcc.2006.05.011

Acute right ventricular (RV) failure following pulmonary embolism (PE) is a strong predictor of poor clinical outcome. Present studies test for an association between RV failure from experimental PE, inflammation, and upregulated chemokine expression. Additional experiments test if neutrophil influx contributes to RV dysfunction. PE was induced in male rats by infusing 24 microm microspheres (right jugular vein) producing mild hypertension (1.3 million beads/100 g, PE1.3), or moderately severe hypertension (2.0 million beads/100 g, PE2.0). Additional rats served as vehicle sham (0.01% Tween 20, Veh). In vivo RV peak systolic pressures (RVPSP) increased significantly, and then declined following PE2.0 (51 +/- 1 mm Hg 2 h; 49 +/- 1, 6 h; 44 +/- 1, 18 h). RV generated pressure of isolated, perfused hearts was significantly reduced in PE2.0 compared with PE1.3 or Veh. MCP-1 protein (ELISA) was elevated 21-fold and myeloperoxidase activity 95-fold in RV of PE2.0 compared with Veh or PE1.3. CINC-1, CINC-2, MIP-2, MCP-1, and MIP-1alpha mRNA also increased in RV of PE2.0. Histological analysis revealed massive accumulation of neutrophils (selective esterase stain) and monocyte/macrophages (CD68, ED-1) in RV of PE2.0 hearts in regions of myocyte damage. Electron microscopy showed myocyte necrosis and phagocytosis by inflammatory cells. LV function was normal and did not show increased inflammation after PE2.0. Treatment with anti-PMN antibody reduced RV MPO activity and prevented RV dysfunction. Conclusions-PE with moderately severe pulmonary hypertension (PE2.0) resulted in selective RV dysfunction, which was associated with increased chemokine expression, and infiltration of both neutrophils and monocyte/macrophages, indicating that a robust immune response occurred with RV damage following experimental PE. Experimental agranulocytosis reduced RV, suggesting that neutrophil influx contributed to RV damage.


Disease Annotations    
pulmonary embolism  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (chemokine (C-C motif) ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Additional Information